A novel homecage operant task reveals circadian dynamics of social motivation in mice

Abstract

Deficits in social motivation are a core feature of many neurodevelopmental disorders, including autism spectrum disorders. While a range of tools have been developed to quantify social motivation in rodents, most rely on brief tests in dedicated apparatuses that can introduce stress and novelty, potentially reducing test reliability. Most current approaches are also typically not suited to studying learning across days or circadian rhythms of social motivation. To address these challenges, we developed a social operant task that can run around-the-clock for multiple days in the mouse homecage, continuously monitoring social motivation around the circadian cycle. The task consists of a custom-built automated door that was installed between two rodent homecages and configured so one mouse could trigger the door to open with a nose-poke action from within their cage. When open, the door allows for social interaction with the neighboring mouse through a perforated stainless-steel panel, which did not allow the mice to cross over into the neighboring cage. Mice opened the door multiple times each day, allowing us to quantify their amount and daily rhythms of social motivation. In our first experiment, C57BL/6J mice (both sexes) were individually housed with an empty adjacent cage for five days, after which a same-sex social partner was introduced for another nine days. Mice opened the door at significantly higher rates when the social partner was present vs. absent, confirming that mice were motivated to earn social interaction. This task also revealed a circadian rhythm to social motivation that peaked about 2 hours after the peak in their feeding rhythm. We speculate that mice first addressed their caloric needs each day before changing their priority to social behavior. Given prior literature implicating the dopamine system in social motivation, we also tested whether dopamine antagonists would block social motivation in our task in a new group of 14 mice (both sexes). The dopamine D1 receptor antagonist SCH23390 (delivered systemically at 0.3mg/kg SC) reduced social seeking without affecting locomotor activity or food intake, demonstrating a selective role for dopamine D1 receptors in social motivation. The dopamine D2 receptor antagonist haloperidol (delivered systemically at 0.3mg/kg SC) also reduced social seeking, but reduced locomotor activity and food intake as well, demonstrating a general reduction in behavior that was not specific to social motivation. Overall, our task offers a way for studying social motivation in the rodent homecage, which has advantages for studying disorders that involve both social and circadian disruptions.